AB0091 INCREASED BIOLOGICAL AGE IN MALE PARTICIPANTS OF SWEDISH AND UK RHEUMATOID ARTHRITIS COHORTS IS NOT LINKED TO DISEASE
Authors: A. Sharma-Oates, N. Rivera, N. Duggal, K. Raza, L. Padyukov, A. Pratt, E. Niemantsverdriet, A. van der Helm-van Mil, S. Jones, J. Lord
Journal: Annals of the Rheumatic Diseases (2022)

Background Immunesenescence in the adaptive immune system, subsequent to thymic involution, results in compromised immunity and increased susceptibility to autoimmune disease and chronic inflammation. There are reports in the literature that immunesenescence, including thymic atrophy and telomere shortening, is accelerated in patients with rheumatoid arthritis (RA)1. What is unclear is whether RA includes accelerated biological ageing overall in addition to immune ageing which may help to explain the increased risk of age-related diseases in RA2. Recent studies have identified a set of DNA methylated sites across the genome that are highly correlated with chronological age and mortality, termed epigenetic clocks3,4 or DNAm age (DNAma), and can be used to determine an individual’s biological age. Objectives The aim of our study is to determine if the biological epigenetic clocks of RA patients are accelerated. Methods We evaluated the Horvath 3 and Hannum 4 epigenetic clocks of control and RA patients using published DNAm data sets, accessions GSE42861 (EIRA, Swedish cohort of 342 RA patients and 328 non-RA controls) and E-MTAB-6988 (77 RA discordant monozygotic twins). Results We did not detect significant differences between DNAma of RA and non-RA twins. Similarly, there were no significant differences between the DNAma of RA patients and controls from the Swedish EIRA cohort. However, we detected a significant acceleration in DNAma of male discordant twins, both RA and non-RA, by 5.4 years (p=3.29e-5) and 2.8 years (p=0.04) using the Hannum and Horvath clocks, respectively. Male participants, both control and RA patients, from the EIRA cohort also exhibited an accelerated DNAma, by 1.5 years (p=7.55e-5) using the Hannum clock but using the Horvath clock a significant DNAma acceleration, by 1.4 years (p=0.002) was detected in male RA patients from the EIRA cohort. Conclusion Overall, we detected a significant biological age acceleration in male participants from both RA and control groups and only found a significant difference between DNAma of Non-RA controls and RA patients for one of the epigenetic clocks. Further analysis using additional cohort data and biological clock algorithms is needed to confirm our findings. References [1]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5. [2]Meune C, et al. (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatol 48:1309-1313. [3]Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115. [4]Hannum G, et al (2013) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell 49:359-367. Acknowledgements The study was funded by FOREUM Disclosure of Interests None declared